The Stooges are crooked gamblers in the Old Western town of Lobo City. Eventually, they are caught cheating the residents (including a tough woodcutter named Pierre (Bud Jamison) ) of a frontier town. They are discovered and must escape into the woods. To elude the sheriff, the Stooges hunt, fish, and disguise themselves as Indians.

However, things start to go wrong when Pierre takes a liking to Curly, who is disguised as an Indian squaw. The two soon get married. A few minutes later, Curly's wig slips off and the trio has to make another run for it. They find what they believe to be a safe place to hide, only to find that they lock themselves right into the Lobo City Jail.

The title Whoops, I'm an Indian! is a play on the stereotype of an Indian battle cry or "war whoop," along with the interjection, "Oops!" denoting surprise. It is also likely a reference to the then-popular song, "I'm an Indian" (1918), composed by Blanche Merrill and most typically covered by Fanny Brice. The song, chronicling a Yiddish girl's marriage to an Indian chief, includes the lines "Look at me, just look at me/Hoo hoo I'm an Indian..."

Of all the Three Stooges shorts, this particular film contains the most amount of Curly's "woo-woo-woo" routine.